人类CXXC5基因在心脏发育早期表达并调控心脏发育，但其具体机制未知。申请者前期研究发现：斑马鱼CXXC5在心脏发育早期强表达，该基因通过负调控心脏前体细胞的数目控制心脏腔室大小的发育，其对心脏发育的调控可能与TGF-β信号通路有关。为了进一步研究CXXC5调控心脏腔室大小的分子机制，申请者拟通过CXXC5基因敲除和转基因斑马鱼模型，研究CXXC5基因调控心肌细胞增殖或调亡的机理，探讨CXXC5基因是否通过TGF-β信号通路调控心脏腔室大小的发育过程。基于申请人鉴定的CXXC5与TGF-β信号激活蛋白Smad2和Smad3有相互作用的基础上，研究CXXC5与Smad2或Smad3通过TGF-β与细胞凋亡信号互作协同调控心脏腔室的大小及调控心肌细胞增殖的分子机理，该研究对揭示CXXC5调控人类心脏发育与疾病的机制具有重要意义。

Studies have shown that the expression of the human CXXC5 gene was related to the regulation of heart development. But the function of CXXC5 in heart development is not clear. The results of applicant preliminary study showed that the CXXC5 was expressed in the early developmental stages of zebrafish heart and regulated the developmental cardiac chamber size through negative regulation of cardiac precursor cell proliferation. And the TGF-β signaling pathway may be related to the regulation of the CXXC5 in the heart development. The applicant intends to study the molecular mechanism of CXXC5 gene regulation in cardiomyocyte proliferation or apoptosis and explore CXXC5 gene function in the TGF-β signaling pathway that regulate the cardiac chamber size, by establishing CXXC5 gene knockout and transgenic experimental model. On the basis of the the preliminary identification of the interaction between CXXC5 and Smad2 or Smad3, TGF-β regulatory proteins, the applicant intends to explore molecular mechanism of synergistic efficacy of the interaction between CXXC5 and Smad2 or Smad3 in the TGF-β signal regulation of the heart chamber size and myocardial cell proliferation or apoptosis. The research is of great significance for CXXC5 function of the human heart development.